OBJECTIVE: To compare the effectiveness and advantages of the double reverse traction reduction versus open reduction internal fixation for treating complex tibial plateau fractures. METHODS: A clinical data of 25 patients with Schatzker type Ⅴ or Ⅵ tibial plateau fractures, who met the selection criteria and were admitted between January 2019 and January 2023, was retrospectively analyzed. Thirteen patients underwent double reverse traction reduction and internal fixation (double reverse traction group), while 12 patients underwent open reduction and internal fixation (traditional open group). There was no significant difference in the baseline data (age, gender, injury mechanism, Schatzker classification, interval between injury and operation) between the two groups ( P>0.05). The effectiveness were evaluated and compared between the two groups, included operation time, intraoperative blood loss, incision length, hospital stay, full weight-bearing time, complications, fracture healing, Rasmussen radiological score (reduction quality), knee Hospital for Special Surgery (HSS) score, and knee flexion/extension range of motion. RESULTS: The double reverse traction group demonstrated significantly superior outcomes in operation time, intraoperative blood loss, hospital stay, incision length, and time to full weight-bearing ( P<0.05). Two patients in traditional open group developed incisional complications, while the double reverse traction group had no complication. There was no significant difference in the incidence of complication between the two groups ( P>0.05). All patients were followed up 24-36 months (mean, 30 months), with no significant difference in follow-up duration between groups ( P>0.05). Fractures healed in both groups with no significant difference in healing time ( P>0.05). At 6 months after operation, Rasmussen radiological scores and grading showed no significant difference between the two groups ( P>0.05); the double reverse traction group had significantly higher HSS scores compared to the traditional open group ( P<0.05). At 12 months after operation, knee flexion/extension range of motion were significantly greater in the double reverse traction group than in the traditional open group ( P<0.05). CONCLUSION Double reverse traction reduction offers advantages over traditional open reduction, including shorter operation time, reduced blood loss, minimized soft tissue trauma, and improved joint functional recovery. It is a safe and reliable method for complex tibial plateau fractures.
Humans ; Tibial Fractures/surgery* ; Fracture Fixation, Internal/methods* ; Male ; Female ; Traction/methods* ; Retrospective Studies ; Middle Aged ; Adult ; Open Fracture Reduction/methods* ; Treatment Outcome ; Range of Motion, Articular ; Fracture Healing ; Operative Time ; Length of Stay ; Blood Loss, Surgical ; Aged ; Tibial Plateau Fractures

Objective:To investigate the detection of the age and pathway and the etiology of sensorineural hearing loss in children, and to guide the early diagnosis. Methods:A retrospective analysis was conducted on the children who passed neonatal hearing screening but were diagnosed with sensorineural hearing loss in our department from January 2019 to September 2022. The clinical characteristics of 66 children with complete medical history, audiology examination, imaging examination and genetic detection of hearing loss were studied. The age group, detection route and degree of hearing loss were analyzed statistically. Results:①The children were aged from 7 months to 12 years old, and most of them were over 3 years old. ②The ways of detection were as follows: 23 cases（34.85%） due to abnormal hearing, 21 cases（31.82%） due to poor language, 15 cases（22.73%） found during physical examination, and 7 cases（10.61%） found with otitis media. Physical examination findings were concentrated in children aged ≤1 year old or 3-6 years old. ③Among the 56 cases, the degree of binaural hearing loss ranged from mild to severe, and most of those within 3 years of age had severe or above hearing loss. There were statistically significant differences in the degree of hearing loss distribution among different detection approaches（P<0.001）. Most children with hearing or language problems had moderate to severe or above hearing loss, and the proportion was significantly higher than that of children detected during physical examination or otitis media. ④There were 21 cases（31.82%） with a pathogenic mutation of GJB2 gene and 9 cases（13.64%） of large vestibular aqueduct syndrome, 7 of which were related to SLC26A4 gene mutation. There were 8 cases（12.12%） with high risk factors of hearing loss. There was 1 case（1.52%） with progressive speech loss after severe infection and high fever and 1 case（1.52%） with unilateral cochlear nerve dysplasia. Conclusion:Delayed hearing loss can occur at all ages and was not easy to be detected in time. The etiology was related to the mutation of deafness-related genes and the high risk factors of hearing loss. Combining hearing and gene screening in childhood, guiding parents to observe children's hearing response and language development, especially strengthening the follow-up of children with high risk factors for hearing loss, is conducive to the early diagnosis of delayed hearing loss.
Humans ; Hearing Loss, Sensorineural/genetics* ; Retrospective Studies ; Child ; Child, Preschool ; Infant ; Connexin 26 ; Male ; Female ; Connexins/genetics* ; Mutation ; Sulfate Transporters ; Hearing Tests

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

Objective:To compare the short-term efficacy between proximal femoral bionic nails (PFBN) and 3G Gamma nails in the fixation intertrochanteric femoral fractures in the elderly.Methods:A retrospective study was conducted to analyze the data of 78 elderly patients with intertrochanteric femoral fracture who had been admitted to Department of Trauma Surgery, The Hospital Affiliated to Qingdao University from October 2021 to December 2022. There were 35 males and 43 females with an age of (76.0±7.9) years. By Evans classification: 6 cases of type Ⅰ, 21 cases of type Ⅱ, 24 cases of type Ⅲ, 23 cases of type Ⅳ, and 4 cases of type Ⅴ. The patients were divided into 2 groups according to their internal fixation methods: a PFBN group of 35 patients fixed by PFBN and a Gamma group of 43 cases fixed with 3D Gamma nails. The time from injury to operation, hospital stay, operation time, intraoperative blood loss, weight-bearing time, fracture healing time, and Harris hip score, visual analogue scale (VAS) and incidence of complications at 6 months after operation were compared between the 2 groups.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). All patients were followed up for (14.0±4.0) months. There were no significant differences between the PFBN and Gamma groups in operation time [(58.9±8.2) min versus (58.1±6.8) min], intraoperative blood loss [(138.0±24.9) mL versus(126.8±25.7) mL], hospital stay [(10.9±2.9) d versus (10.3±4.0) d],fracture healing time [(5.0±1.3) months versus (5.1±1.3) months], or good and excellent rate by the Harris hip score [82.9% (29/35) versus 76.7% (33/43)], VAS score [0(0, 1) points versus 1(0, 1) points], or incidence of complications at 6 months after operation [2.9% (1/35) versus 4.7% (2/43)] (all P>0.05). However, the complete weight-bearing time for the PFBN group was (5.3±1.2) weeks, significantly earlier than that for the Gamma group [(6.9±1.4) weeks] ( P<0.05). Conclusion:In the fixation of intertrochanteric femoral fractures in the elderly patients, both PFBN and 3D Gamma nails can achieve satisfactory short-term efficacy, but PFBN is more beneficial to the functional recovery of the hip joint because it leads to earlier complete weight-bearing time than 3D Gamma nails.

Objective:To evaluate the application of the standard of "Delimitation and Classification of Keshan Disease Areas" (GB 17020-2010, Standard for short), learn about the applicability of its technical indicators and requirements, and provide a basis for revision of the Standard.Methods:In March 2022, provinces with severe epidemic areas of Keshan disease or new cases reported in recent years were selected, including Gansu Province, Inner Mongolia Autonomous Region, Shandong Province, Shaanxi Province, Yunnan Province, Shanxi Province, Liaoning Province, and Chongqing City. Multi-stage stratified sampling method and questionnaire survey were adopted to collect information on the application of Standard by relevant health institutions.Results:A total of 448 questionnaires were collected, including 445 valid. The survey results showed that 87.64% (390/445) of the respondents were aware of the Standard, and 64.72% (288/445) had received training on the Standard. Eighty-two point two per cent (365/445) of the respondents believed that the Standard was simple and easy to operate, 83.82% (373/445) believed that the determination of the diseased townships was scientific and reasonable, and could be effectively implemented, and 83.60% (372/445) believed that the determination of historical epidemic areas was applicable to the current situation of Keshan disease; 38.88% (173/445), 38.20% (170/445), and 37.98% (169/445) of the respondents believed that the classification indicators for classifying epidemic areas (severe, moderate, and mild epidemic areas) were not applicable to the current situation of the disease in the local or provinces with Keshan disease, respectively. Among the indicators for epidemic areas classification, 30.79% (137/445), 29.21% (130/445), and 28.54% (127/445) of the respondents thought that the annual prevalence, the annual number of new cases and the annual incidence were most suitable for classification of Keshan disease areas.Conclusions:The Standard has been applied well in practice. However, based on the current situation of Keshan disease, it is suggested to redefine the standard for the severity of the disease and the classification of historical epidemic areas.

Objective:To summarize the best evidence for external auditory canal irrigation in patients with cerumen embolism.Methods:The clinical decisions, guidelines, systematic reviews, expert consensus, group standards, evidence summaries, and randomized controlled trials regarding external auditory canal irrigation in patients with cerumen embolism were retrieved from databases and websites such as BMJ Best Practice, UpToDate, Guidelines International Network, National Institute for Health and Clinical Excellence, Joanna Briggs Institute Evidence-Based Health Care Center Database, PubMed, Embase, China National Knowledge Infrastructure, WanFang data, and China Biology Medicine disc. The search period was from database establishment to February 15, 2023. Six researchers screened the literature, evaluated the methodological quality, and extracted and summarized the best evidence for external auditory canal irrigation in patients with cerumen embolism.Results:A total of nine articles were included, including one clinical decision, two guidelines, two systematic reviews, one group standard, and three randomized controlled trials. Sixteen pieces of evidence were summarized from six aspects of operators: pre-operation evaluation and preparation, operation process, post-operation handling, health education, and adverse reactions during operation.Conclusions:This paper summarizes the best evidence for external auditory canal irrigation in patients with cerumen embolism. Medical and nursing staff should carefully select and apply evidence based on clinical scenarios and patient's wishes.

Invasive fungal infections play an important factor threatening human health.In recent years, the number of the susceptible population of invasive fungal infections has increased rapidly, leading to a significant increase in the disease burden of human fungi.In 2022, the World Health Organization released a list of key fungal pathogens, aiming to promote global research and investment in fungal infection and antifungal resistance.At present, antifungal drugs are preferred for anti-fungal infection treatment, although the efficacy is limited by the adverse events and drug resistance.Improving the damaged host immune response is a reasonable way to improve the effectiveness of antifungal drugs.This article briefly described the epidemiology of fungal infections, summarized how hosts mediate the clearance of fungi by initiating innate and adaptive immune responses, and discussed the prospects and clinical evidence supporting immunomodulatory therapy for invasive fungal infections.